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Aim of this study was to identify mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> signatures associated with stages of disease progression in patients with chronic viral hepatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression profile was investigated in liver biopsies from patients with chronic viral hepatitis and correlated with clinical, virological and histopathological features. Relevant mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s were further investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Most of the significant changes in mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression were associated with liver fibrosis stages and included the significant up\u2010regulation of a group of mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s that were demonstrated to target the master regulators of epithelial\u2013mesenchymal transition <jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>2 and involved in the preservation of epithelial cell differentiation, but also in cell proliferation and fibrogenesis. In agreement with mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> data, immunostaining of liver biopsies showed that expression of the epithelial marker E\u2010cadherin was maintained in severe fibrosis\/cirrhosis while expression of <jats:styled-content style=\"fixed-case\">ZEB<\/jats:styled-content>s and other markers of epithelial\u2013mesenchymal transition were low or absent. Severe liver fibrosis was also significantly associated with the down\u2010regulation of mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s with antiproliferative and tumour suppressor activity. Similar changes in mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and target gene expression were demonstrated along with disease progression in a mouse model of carbon tetrachloride (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l4)\u2010induced liver fibrosis, suggesting that they might represent a general response to liver injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Chronic viral hepatitis progression is associated with the activation of mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> pathways that promote cell proliferation and fibrogenesis, but preserve the differentiated hepatocyte phenotype.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12737","type":"journal-article","created":{"date-parts":[[2014,11,24]],"date-time":"2014-11-24T08:22:54Z","timestamp":1416817374000},"page":"1324-1333","source":"Crossref","is-referenced-by-count":12,"title":["Changes in micro<scp>RNA<\/scp> 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